Abstracts

Rationale: USL255, Qudexy™ XR (topiramate) extended-release capsules, was recently approved as a once-daily treatment for epilepsy (monotherapy for partial-onset seizures [POS] or primary generalized tonic-clonic [PGTC] seizures in patients ≥10 yr; adjunctive therapy for POS, PGTC, or seizures associated with Lennox-Gastaut syndrome in patients ≥2 yr). USL255 demonstrated efficacy and favorable tolerability for the adjunctive treatment of refractory POS in a randomized, double-blind, placebo-controlled, global, phase 3 study (PREVAIL; NCT01142193). Long-term safety and efficacy of USL255 were evaluated in a 1-year PREVAIL open-label extension (OLE; NCT01191086) study. Provided here are long-term efficacy data from the OLE. Methods: Patients who completed the 11-week double-blind treatment phase from PREVAIL were eligible to enroll in the OLE. Participants underwent a 3-week blinded-conversion phase, during which patients randomized to placebo in PREVAIL were titrated to 200 mg/d USL255 (50 mg/wk) and those randomized to 200 mg/d USL255 in PREVAIL were given matching placebo. The conversion phase was followed by a 52-week open-label treatment phase. After 11 weeks of treatment, changes in USL255 dosage (in 50 mg/wk increments up to a maximum of 400 mg/d) and concomitant AEDs were allowed. Efficacy assessments included median percent reduction from baseline in weekly POS frequency and responder rates (proportion of patients with ≥50%, ≥75%, or 100% reduction in weekly POS frequency). The 8-week baseline period prior to the start of treatment in PREVAIL was also used as the baseline for the OLE. Results: Of the 217 patients who completed PREVAIL, 210 (96.8%) enrolled in the OLE. A total of 148 patients (70%) completed the OLE; the most common reasons for discontinuation were voluntary withdrawal by patient (11%) and adverse events (9.5%). During the first 3 weeks (conversion phase) of USL255 treatment, median percent reduction in POS frequency was 51%. Efficacy of USL255 was maintained throughout the study, as median percent reduction in POS frequency was 59% over the entire 52-week open-label phase. Similar results were observed for 50% responder rates, which were 52% over the first 3 weeks of treatment and 62% over the entire open-label phase. When evaluating efficacy by 12-week intervals, reduction in seizure frequency and 50% responder rate values were similar in each interval to those observed during the entire open-label phase. The 75% and 100% responder rates for all patients during the entire 52-week open-label phase were 32% and 5%, respectively. Conclusions: Within the 1-year PREVAIL OLE, treatment with up to 400 mg/d of USL255 was associated with a reduction in seizure frequency and maintenance of efficacy in patients with refractory POS. The long-term results are similar to those with USL255 treatment in the double-blind PREVAIL study and suggest that once-daily USL255 may provide long-term benefits for the treatment of epilepsy. Supported by Upsher-Smith Laboratories, Inc.